The lower vertebrates, amphibia in particular, offer excellent model systems for studying immunity. During the past eight years, we have explored a variety of regulatory mechanisms of humoral immune responses in representative amphibians. We have been initially concerned with learning which regulatory mechanisms, e.g. amplification, suppression, phagocytic cell control, memory, etc., exist in primitive forms and then to attempt to understand their causality. Our hope has been that at least some of them may involve less sophisticated interactions than those presently known for mammalian systems. Thus they may provide insights into immune phenomena only poorly understood for man. The amphibian model systems reflect an evolutionary, a developmental, and a functional immunologic progression likely to relate to the transition from an aquatic to terrestrial habitat. The three amphibia we have used (primitive to advanced) are (1) the common American newt, Notophthalmus viridescens, (2) Xenopus, laevis, the South African clawed toad, and (3) Rana pipiens, the American grass frog.